The objective of this research is the elucidation of the molecular events in tumor cells of pituitary and nonpituitary origin by which the synthesis, storage, and secretion of certain polypeptide hormones are regulated. In particular, it is concerned with the biosynthetically-related ACTH/beta LPH series of hormones: adrenocorticotropin (ACTH), beta-lipotropin (beta LPH), gamma-lipotropin (gamma LPH), beta-melanocyte-stimulating hormone (beta MSH), and beta-endorphin (beta END). Because nonpituitary secretion of the ACTH/beta LPH peptides is often associated with that of calcitonin (CT) and arginine vasopressin (AVP), these polypeptides will also be investigated. An ACTH-secreting small cell lung carcinoma tissue culture cell line will be used to study intact-cell synthesis and processing of the ACTH/beta LPH precursor, to provide mRNA for in vitro cell-free translation of the ACTH/beta LPH precursor, and for synthesizing ACTH/beta LPH precursor cDNA to be inserted and amplified in recombinant DNA plasmids in order to determine its nucleotide sequence. The mechanisms of ectopic hormone secretory "autonomy" will be explored. The potential clinical applicability of simultaneous plasma ACTH, LPH, beta END, CT and AVP determinations under optimal conditions as noninvasive ambulatory diagnostic test for lung carcinoma will be explored, as will the possibility that these hormones are secreted by normal and/or diseased nonneoplastic pulmonary cells; using both radioimmunoassay and immunocytochemistry. Human pituitary proATCH/beta LPH will be further purified and characterized, and the syndrome of tumor secretion of ACTH/beta LPH peptides will be further explored in animal models. The ultimate aim of this research is to understand the relationship between abnormal hormone synthesis and the mechanism of malignant transformation.